Metabolic changes after surgical operations, with special reference to disturbances in protein, chloride, sodium and water metabolism after partial gastrectomy, and to the use of protein hydrolysates

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(1) An investigation has been undertaken of certain post- operative metabolic disturbances in 59 surgical patients, and in 41 of these cases nitrogen balance studies were carried out. Control observations were also made on four healthy volunteers submitted to two types of food restriction, and on one patient who was not subjected to operation.

(2) It was found that after gastrectomy in well- nourished subjects there was an increase in urinary nitrogen excretion which lasted for from five to eight days, the maximum loss of nitrogen being on the second to fifth days. During the same period the reduction in food intake combined with this increased excretion of nitrogen resulted in a period of negative nitrogen balance. Extension of the duration of this period of negative nitrogen balance beyond the minimum was related to protein and caloric intake or to complications, such as wound infection, broncho- pneumonia or superficial phlebitis.

(3) In mal- nourished subjects there maybe no post -operative increase in urinary nitrogen excretion, or this may be much less severe than in well -nourished subjects.

(4) The consumption of a high protein high calorie diet before operation has a variable effect on body weight: it is not, related in any consistent manner to nitrogen retention, and does not alter the response to operation in any significant way in well-nourished subjects. The catabolic phase is in no way diminished. An increase in the intake of calories after opera tion may accelerate the restoration of nitrogen equilibrium or positive balance. An increase in the protein intake without a proportionate increase in calories may lead to wastage of the protein. There is a physical limit to the quantity of food 'which may be eaten after gastrectomy, but this is much in excess of the diet which is usually provided.

(5) The oral consumption of protein hydrolysate (such as pronutrin) was employed to increase the quantity of protein ingested. In the form at present available, such hydrolysates offer a compact means of administering protein if the patient can tolerate the smell and taste of the preparation.

(6) Protein hydrolysates in the form of casydrol or amigen were administered by the intravenous route to 22 patients. In five of these detailed studies of the quantities of total nitrogen and the amino acid nitrogen excreted in the urine were made. The urinary amino acid nitrogen excretions during and after casydrol infusions were compared with those found in a control series of patients submitted to gastrectomy, and in a series of volunteers. About 60 per cent. of the amino acid nitrogen administered by the intravenous route as casydrol, and about 90 per cent. in the case of amigen, was apparently retained) in the body for metabolism. After gastrectomy, well- nourished subjects to whom casydrol or amigen was given by the intravenous route, excreted in addition to the increased quantity of nitrogen normally expected from protein catabolism, an amount of nitrogen about about equal to that administered as hydrolysate. In the remaining patients, no apparent benefit was obtained by the infusion of casydrol, except in one who was suffering from the effects of prolonged restriction of food consumption. Provided that a rate of 100 to 150 ml. per hour is not exceeded, casydrol does not cause nausea or other disturbances when administered by the intravenous route, and thrombosis and phlebitis are not more frequent than with 5 per cent, glucose solution alone. The few indications for the use of casydrol by the intravenous route which still appear to be justifiable on theoretical grounds, such as prolonged starvation or ulcerative colitis, require further examination by clinical trial.

(7) Human plasma was administered to two patients as the sole source of protein. This method of supplying protein is condemned as unsound in conception and unsafe in practice.

(8) After partial gastrectomy, the prevention of starvation throughout the post -operative period was achieved in three out of six patients in whom it was attempted by the administration of adequate quantities of protein and calories as milk mixture by jejunal tube or by mouth. There was still an increase in urinary nitrogen excretion, that is to say, the catabolic phase was not abolished. The negative nitrogen balance over the period of ten days after operation was, however, greatly reduced, being smaller than after any other procedure.

(9) After partial gastrectomy there is usually some degree of haemodilution and increase in plasma volume indicated directly by measurement, and indirectly by reduction in haematocrit
- 21 7 - haematocrit red blood corpuscles and haemoglobin concentration. There is often a reduction in plasma albumin concentration and a rise in plasma globulin concentration which may equal or exceed the change of albumin concentration. There are other and probably more important changes in the total quantities of these proteins in active circulation in the plasma. There is a contemporary shift of chloride from red blood corpuscles to plasma. There was no consistent change in plasma amino acid nitrogen, non -protein nitrogen or blood urea nitrogen concentra- tions even during or after hydrolysate infusions.

(10) The observation of a reduction in urinary chloride excretion during the first six to eight days after major surgical operations led to further investigation and to a demonstration of a coincidence of reduction in urinary chloride excretion with the increased nitrogen excretion of the catabolic phase. Further investigation has revealed that following operation there is a retention in the body of chloride, sodium and water which is largely independent of the source or quantity of sodium and chloride, or the route by which they are made available.

(11) There is no relationship between weight loss and nitrogen balance; this is probably due to changes in water and electrolyte balance masking the effects of nitrogen retention on loss of weight. After operation there appears to be a steady loss of body tissue which also for several days may be masked to some extent by water retention.

(12) The possible clinical applications of these observations have been discussed and further hopeful lines of extension have been suggested.